Cultured hippocampal neurons from fetal trisomy 21 (Ts21) in humans results in numerous phenotypic abnormalities collectively known as Down syndrome (DS). As there is substantial genetic homology between regions of human chromosome 21 and mouse chromosome 16, the trisomy 16 (Ts16) mouse is studied as a potential model for DS. In both fetal human Ts21 and murine Ts16 brain, developmental abnormalities were detected. Individual neuronal electrical activity and the action of neurotrophic factors (e.g., NGF) are two determinants of precise brain wiring. As Ts16 mice die in utero, it is necessary to use a cell culture system to assess the effect of Ts16 on development and maturation. Using electrophysiological and cell-culture techniques we are investigating excitable neuronal tissue from the central nervous system (CNS) (hippocampus, basal forebrain) and peripheral nervous system (PNS) (dorsal root ganglion (DRG)), as well as nonneuronal excitable tissue (muscle). Specific ongoing projects includes: 1) Measurements of sodium current in hippocampal cultured neurons; 2) Measurements of calcium current in hippocampal cultured neurons. 3) Assessment of the effects of NG on DRG neurons; 4) Measurements of morphological and electrical properties of septal neurons; 5) Neuro-muscle coculture system as a model of cholinergic synapse; 6) Fine structural studies of the hippocampus and DRG in 16 day old mouse embryos and hippocampal grafts.